tbuckley/cabot-search huggingface dataset:
GCT-21. Long-term outcome and follow up of intracranial germ cell tumors: Reduced-dose radiotherapy and intensified chemotherapy improves clinical outcome and quality of life for long-term survivors
Authors: Naoki Kagawa, Takako Miyamura, Kai Yamasaki, Ryuichi Hirayama, Noriyuki Kijima, Yoshiko Okita, Tomoyoshi Nakagawa, Junichi Hara, Haruhiko Kishima
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Intracranial germ cell tumors (iGCT) are heterogeneous tumors with several histopathology. Chemoradiotherapy is effective and required for treatment against them, but optimal treatment intensity should be selected from the viewpoint of both improvement of clinical outcome and avoidance of late complications. We introduced a protocol with reduced-dose radiotherapy and intensified chemotherapy for iGCT. OBJECTIVE: We retrospectively analysed the clinical outcome, especially for non-germinomatous germ cell tumors and long-term clinical outcome of late complications, enrollment and employment, as indicators of quality of life (QOL). MATERIALS AND METHODS: Thirty-eight children and young adults (28 men and 10 women) with iGCTs treated in our institution from 1997 to 2013 were enrolled in this study. They consisted of 26 germinomas including HCG-producing cases and 12 non-germinomatous GCTs (NGGCT). Local irradiation was selected for all patients, and the dose of irradiation was 23.4-54 Gy. The whole-brain irradiation was made in patients who had intracranial dissemination, but any prophylactic irradiation to the whole brain and spinal cord was not performed. For NGGCT, high-dose chemotherapy and peripheral blood stem cell transplantation (PBSCT) were introduced. Second-look surgeries were performed for cases with residual tumors after induction chemotherapies. RESULTS: In germinoma group and NGGCT group, 10-year progression-free survival was 86% and 84%, 10-year overall survival was 93% and 91%, respectively. About late complications, endocrinological replacement (39%), cerebrovascular disease such as cavernous hemangioma and arterial stenosis (18%), secondary neoplasm (2.6%) were observed. Regarding QOL, enrollment and return to school rate was 92% and employment and the return rate was 89%, which were influenced by hemipararesis associated with basal ganglia lesion, intractable epilepsy and whole-brain irradiation. CONCLUSION: Reduced-dose radiotherapy and intensified chemotherapy for iGCT, especially NGGCT, improved the clinical outcome and QOL of long-term survivors, suppressing late complications. Further comprehensive follow-up and analysis are needed.
The role of tachycardia and beta-adrenergic stimulation in inducing early cardiac remodelling
Authors: M Kiessling, N Djalinac, I Matzer, J Voglhuber, S Ljubojevic-Holzer
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Foundation. Main funding source(s): BioTechMed Graz Objective Cardiac remodelling encompasses changes at the molecular, cellular and gene expression level following pathologic insult to the heart. Initially, it maintains cardiovascular homeostasis and allows patients to remain asymptomatic, but if untreated, it eventually progresses to symptomatic heart failure. Excessive β-adrenergic stimulation and tachycardia are potent triggers of cardiac remodelling; however, the underlying mechanisms of their cellular effects are not fully understood. Using neonatal rat ventricular cardiac myocytes (NRVCMs), we studied individual and synergistic potency of ß-adrenergic stimulation and tachycardia to modulate pathological gene expression profiles, as well as the effectiveness of ß-blockers (BB) in preventing these alterations. Methods Primary NRVCMs were isolated from 1-day-old neonatal Wistar rats, cultured for 3 days and subsequently stimulated for 3h at basal (1Hz) and tachycardia (8Hz) conditions either in (1) cell culture medium to determine the sole effect of tachycardia, (2) cell culture medium supplemented with ß-adrenergic agonist isoprenaline (ISO; 10µM) to investigate the influence of ß-adrenergic stimulation and signalling or (3) cell culture medium supplemented with ISO following 1h preincubation with propranolol (ISO+BB; 1µM) to assess the potential of BB in preventing gene reprogramming. Screening of relative mRNA levels of hypertrophic marker genes and regulators of ion homeostasis in cardiomyocytes was performed by qPCR and calculated using the 2-ΔΔCt quantification method. Results qPCR screening of the known hypertrophic marker genes revealed that tachycardia caused significant transcriptional upregulation of regulator of calcineurin 1 (RCAN1) and interleukin-6 receptor (IL6R). Treatment with ISO additionally upregulated RCAN1, while preincubation with BB resulted in a return towards baseline expression of both genes, completely blocking the effects of tachycardia alone or when combined with ISO stimulation. Interestingly, two potassium channel genes, KCNH2 and KCNJ2, responsible for expression of hERG and Kir2.1 channels, respectively, were unchanged with tachycardia alone but significantly downregulated upon additional stimulation with ISO. Preincubation with BB could - at least partially - reverse the effect. Conclusion In conclusion, we could show that apart from the well-documented effect of excessive ß-adrenergic stimulation on hypertrophic signalling in cardiomyocytes, it also has a direct, non-tachypacing mediated effect on the expression levels of hERG and Kir2.1 potassium channels, which may be causally involved in inducing early cardiac remodelling. Thus, a previously unidentified benefit of BB therapy may be restoring potassium homeostasis contributing to the prevention of adverse cardiac remodelling and its progression to heart failure.
Complications after transrectal ultrasound guided biopsies in screening for prostate cancer with PSA followed by MRI – results from the Göteborg prostate cancer screening 2 trial
Authors: K. Kohestani, R. Arnsrud Godtman, A. Assadi, K. Eriksson, J. Stranne, J. Wallström, M. Hellström, J. Hugosson
Journal: European Urology (2022)
How common is generalised pustular psoriasis ( <scp>GPP</scp> ) in Sweden?
Journal: British Journal of Dermatology (2022)

Generalised pustular psoriasis (GPP) is a rare but serious type of psoriasis. GPP causes puss‐filled blisters, usually over the whole body. GPP can occur on its own, or together with psoriasis vulgaris, the most common type of psoriasis.
IMG-10. Determining brain tumour grade non-invasively using a simplified MRI perfusion protocol: single-bolus, leakage-corrected dynamic susceptibility-contrast MRI
Authors: Stephanie Withey, Lesley MacPherson, Adam Oates, Stephen Powell, Jan Novak, Simon Bailey, Dipayan Mitra, Theodoros N Arvanitis, Omar Khan, Heather E L Rose, Lara Worthinton, Andrew C Peet
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: Perfusion is associated with grade and survival in children’s brain tumours. Dynamic susceptibility-contrast (DSC-) MRI measures perfusion non-invasively, estimating relative cerebral blood volume (rCBV). We previously showed significant differences between pre-treatment rCBV in low- and high-grade tumours in a multicentre study. Contrast agent leakage from tumour vessels during acquisition affects rCBV accuracy. A contrast agent pre-bolus can be given but this can be challenging in a clinical environment, introducing variability. Alternatively, a single bolus can be administered with leakage correction applied when processing the data. We investigated pre-treatment rCBV values in a multicentre study without pre-bolus administration. METHODS: Thirty-six patients underwent pre-treatment DSC-MRI scans at 2 centres on 4 different scanners. Protocols were variable. Pixel-by-pixel contrast agent concentration time courses were analysed. Maps of uncorrected (rCBVuncorr) and leakage-corrected rCBV (rCBVcorr) were produced. Whole-tumour regions-of-interest were defined and median whole-tumour DSC-MRI parameters calculated. Patients subsequently underwent surgery / biopsy. Tumours were classified and graded. RESULTS: Twelve tumours were classified as low-grade; 24 as high-grade. Median whole-tumour rCBVuncorr was significantly higher in high-grade tumours than in low-grade tumours (1.628 vs -0.167, p&amp;lt;0.001). Median rCBV significantly increased in low-grade tumours following leakage correction (-0.167 to 1.072, p=0.007); there was no significant change for high-grade tumours. Using the median rCBVuncorr of 1.19 to differentiate between low- and high-grade tumours resulted in sensitivity and specificity of 75% and 100%, respectively; median 1.45 for rCBVcorr resulted in sensitivity and specificity of 67% and 100%, respectively. DISCUSSION: DSC-MRI measures of perfusion can distinguish between low- and high-grade paediatric brain tumours. Contrast agent leakage correction is essential for accurate measurement of rCBV. This is robust across multiple centres despite using multiple protocols. CONCLUSION: Pre-treatment multicentre perfusion MRI acquired with a single-bolus and contrast agent leakage correction can aid with differentiating between high- and low-grade paediatric brain tumours.
Risk of hepatitis C reinfection following successful therapy among people living with HIV: a global systematic review, meta-analysis, and meta-regression
Authors: Samira Hosseini-Hooshyar, Behzad Hajarizadeh, Sahar Bajis, Matthew Law, Naveed Z Janjua, Daniel S Fierer, David Chromy, Jürgen K Rockstroh, Thomas C S Martin, Patrick Ingiliz, Chien-Ching Hung, Gregory J Dore, Marianne Martinello, Gail V Matthews
Journal: The Lancet HIV (2022)
A real-world experience of combined treatment with romidepsin and azacitidine in patients with peripheral T-cell lymphoma.
Authors: Matko Kalac, Constantine Si Lun Tam, Mendel Goldfinger, Zhengrui Xiao, Sridevi Rajeeve, Francesca Montanari, Jennifer Ann Kanakry, Owen O'Connor, Enrica Marchi
Journal: Journal of Clinical Oncology (2022)

e19550 Background: Patients with peripheral T-cell lymphoma (PTCL) lack good treatment options, particularly in the relapsed and refractory setting. Our work suggested that epigenetic therapies can be safe and effective for patients with PTCL, particularly those with T-cell lymphomas with a follicular helper (TFH) phenotype. It is thought that recurrent mutations in epigenetic factors, including Ten-Eleven Translocation-2 (TET2), DNA methyl transferase-3A (DNMT3A) and isocitrate dehydrogenase-2 (IDH2) may contribute to PTLC vulnerability to epigenetic drugs. Methods: Objective of this study was to evaluate the merits of romidepsin plus subcutaneous azacitidine in patients with PTCL when administered in a ‘real-world’ scenario. We retrospectively identified 17 PTCL patients world-wide that were treated with azacitidine and romidepsin outside of a clinical trial based upon queries regarding off study use. The study was reviewed and approved by each Medical Center Institutional Review Board. Their pretreatment characteristics are shown in Table. Results: Eleven patients had angioimmunoblastic lymphoma (AITL), 2 had adult T-cell leukemia/lymphoma (ATLL), 2 had TFH PTCL, 1 had PTCL-NOS and 1 had composite lymphoma (TFH PTCL with diffuse large B cell lymphoma). Ten patients had next generation sequencing performed. Most common mutations found were those of TET2 (7 pts), RHOA (4pts), IDH2 (3pts) and DNMT3A (1 pt). One ATLL patient had mutations in TRAF3, FAT1 and MED12. Among these 17 patients, overall response rate (ORR) was 76% and the complete response rate (CR) was 52%. Median number of cycles was 4 (range 1-12). Treatment was well tolerated but notable adverse effects included nausea, fatigue, rash, neutropenia and thrombocytopenia. One patient experienced febrile neutropenia while another had pulmonary infiltrates (differential diagnosis included drug toxicity versus infection). In 4 patients, azacitidine and romidepsin were used to achieve remission prior to allogeneic transplant (range of cycles 1-3), with all 4 patients were in CR at their last disease assessment. Conclusions: Subcutaneous azacitidine and romidepsin administered in a ‘real-world’ situation is highly effective in patients with relapsed PTCL with tolerable toxicity, and can be used to successfully bridge patients to stem cell transplant.[Table: see text]
Smoking cessation after cancer diagnosis: Relationships matter.
Authors: Melissa Francoise Neumann, Neal J Murphy, Nagashree Seetharamu
Journal: Journal of Clinical Oncology (2022)

e24039 Background: Continued smoking after a cancer diagnosis leads to worse morbidity and mortality. Unfortunately, smoking prevalence remains high amongst cancer patients and survivors. Few studies have been conducted to evaluate and target patients’ social networks that may contribute to a patient continuing to smoke. We developed a questionnaire intended to assess patients’ smoking status, motivation to quit, patient/family dynamics, and interest in enrolling in a smoking cessation program that includes the patient and the person closest to them in their social network that may be contributing to their continued smoking. Methods: We designed a three-page questionnaire to gain more information about a patient’s past and current smoking history, level of nicotine dependence, assessment of their motivation to quit smoking, their social network and family/friends who may be smoking, and willingness of the patient and close family to quit. Inclusion criteria included patients who have been diagnosed with any solid tumor malignancy and had a history of smoking or recently quit. Non-smokers were excluded. IRB approval was obtained and questionnaires were distributed to patients when checking in at the front desk of the Monter Cancer Center. 32 questionnaires were collected from July 2021 - January 2022. Results: Of the questionnaires completed, 59% quit smoking after their cancer diagnosis, 34% tried and were unable, and 7% did not try or declined to answer. Of the 59% who quit, 52% were married, compared to 45% of the 34% who tried and were unable to quit. The odds of quitting among people who were married was 1.56 (95% CI 0.36 - 6.69; p-value 0.55) times the odds of quitting among people who were not married. In the quit group, 53% lived with a smoker at some point compared with 75% of those in the quit but unable to group. The odds of quitting among people who lived with a smoker was 0.42 (95% CI 0.08 - 2.07; p-value 0.28) times the odds of quitting among people who did not live with a smoker. Five social network members quit after their relatives’ cancer diagnosis. No patients were currently enrolled in a tobacco cessation program. Two people answered they would be interested in being enrolled in a tobacco cessation program with a close family member that also smokes. Conclusions: Our study highlights high rates of continued smoking amongst cancer patients. Being diagnosed with cancer can serve as a teachable moment and motivate patients to quit smoking. Social network plays an important role in tobacco cessation. Our study showed that the odds of quitting was lower in patients who lived with smokers than those who did not, though not statistically significant likely due to small sample size. None of the active smokers were enrolled in a smoking cessation program highlighting the imminent need for innovative smoking cessation platforms that are engaging and effective in improving quit rates amongst cancer patients.
Impact of node count on survival outcomes of lymph node dissection in non-metastatic upper tract urothelial carcinoma: Analysis of the robuust registry
Authors: K. Hakimi, U. Carbonara, H. Djaladat, R. Mehrazin, D. Eun, A. Reese, M. Gonzalgo, V. Margulis, R. Uzzo, J. Porter, C. Sundaram, F. Abdollah, A. Mottrie, R. Tellini, M. Ferro, M. Meagher, A. Saidian, A. Walia, A. Veccia, A. Ghoriefi, G. Cacciamani, A. Bhattu, A. Minervini, R. Autorino, I. Derweesh
Journal: European Urology (2022)
Innovative endoscopic submucosal dissection for early gastric neoplasm using intralesional traction and snaring techniques
Authors: Yoshihisa Shoguchi, Mitsuru Esaki, Yosuke Minoda, Xiaopeng Bai, Haruei Ogino, Eikichi Ihara, Yoshihiro Ogawa
Journal: Endoscopy (2022)

Various assistive techniques have emerged to improve the treatment outcomes of endoscopic submucosal dissection (ESD) for gastric neoplasms [1] [2] [3] [4] [5]. We report a novel use of assistive intralesional traction, combined with snaring, for gastric ESD ([Fig. 1 a]).
Urinary exosome microRNA signatures as a noninvasive prognostic biomarker for prostate cancer
Authors: H.J. Kwon, C.E. Yoon, D. Shin, S. Shin, H.W. Moon, H.J. Cho, U. Ha, S. Hong, J.Y. Lee, Y-J. Chung, S.W. Kim, Y.H. Park
Journal: European Urology (2022)
Nanobodies as novel potential drugs to target cardiac light chain amyloidosis
Authors: L Broggini, M Giono, V Speranzini, MM Barzago, G Palladini, L Diomede, C Pappone, S Ricagno
Journal: Cardiovascular Research (2022)

Abstract Funding Acknowledgements Type of funding sources: Private hospital(s). Main funding source(s): IRCCS GRUPPO SAN DONATO Light chain amyloidosis (AL) is a systemic disease where fibrillar deposition of misfolded immunoglobulin light chains (LCs) severely affects organ functions. Cardiac involvement (75% of all AL cases) results in the worst prognosis for patients (1). Current AL therapies rely on repurposing of chemotherapeutic drugs targeting plasma cells as the source of LCs; however patients with cardiac damage are often too compromised to sustain such regiments. Alternative approaches aimed at destroying AL fibrils are being evaluated in clinical trials. Nevertheless, none of these treatments offer reliable solutions to counteract the life-threatening cardiac involvement in AL (2). Here, we propose an alternative approach targeting soluble toxic LCs: these immunoglobulin fragments are frequently overexpressed in patients with cardiac damage and have been found to exert toxicity to cardiac cells, making them an ideal candidate as new drug targets for cardiac AL (3). We combined a multidisciplinary approach to scout for and probe next generation AL drugs based on nanobodies designed to specifically bind soluble toxic LCs. Compared to conventional monoclonal antibodies, nanobodies consist of just two heavy chains, with a single variable domain (VHH, ~15kDa) as the antigen-binding region. These nanoscale VHHs can retain full antigen-binding potential upon isolation, establishing them as the smallest, naturally-derived antigen-binding fragment (4). To reach our aim, 11 different nanobodies against a cardiotoxic light chain (H3), derived from patient suffering from AL (5), were produced and characterized. To identify the most promising among the pool, a detailed characterization of the in vitro binding between H3 and each nanobody was performed, using a series of biophysical techniques, including isothermal titration calorimetry, microscale thermophoresis, bio-layer interferometry, and multi-angle light scattering. Notably, all the nanobodies efficiently bind to H3 forming stable complexes. Then, to investigate the capability of nanobodies to prevent H3 cardiotoxicity, we used the nematode C. elegans as in vivo model. Indeed, in C. elegans the administration of cardiotropic LCs causes a profound functional and structural damage on the pharynx, considered an "ancestral heart" (6). Interestingly, we found that some of our nanobodies prevented H3 from exerting its toxic activity, as their presences preserve nematode functional parameters. Collectively, our data pinpointed the novel potential role of nanobodies in the development of alternative treatments of AL patients with cardiac involvement.
Prognostic effect of TP53 mutation combined with EGFR mutation or KRAS mutation on non-small cell lung cancer.
Authors: Ying Li, Da Jiang, Xuhui Niu, Xinliang Zhou, Lei Hong, Yanzhi Cui, Ke Shi, Hui Jin, Xue Zhang, Fang Huang, Wenya Song, Shaoshuang Fan, Ruoying Deng
Journal: Journal of Clinical Oncology (2022)

e21046 Background: To explore the prognostic value of TP53 co-mutation with EGFR or KRAS in advanced non-small cell lung cancer. Methods: 314 patients with advanced non-small cell lung cancer (NSCLC) admitted to the Department of Oncology of the Fourth Hospital of Hebei Medical University from January 2016 to January 2021 were retrospectively analyzed, all with complete genetic information.According to the analysis results, EGFR and KRAS were identified as co-mutated genes.TP53 mutation was used as the experimental group and TP53 wild as the control group.Patients in TP53 mutation group were further classified and discussed according to different exon 4, 5, 6, 7, 8, other mutations and mutations could not be classified.Co-mutation group was studied according to TP53/KRAS mutation status, and according to KRASG12 mutation, Patients were divided into TP53/KRASG12C (wt/wt), TP53/KRASG12C (wt/mut), TP53/KRASG12C (mut/mut) and TP53/KRASG12C (mut/mut) for further grouping.In the study of TP53/EGFR co-mutation, TP53/EGFR mutation status was divided into groups, and subgroup analysis was conducted according to different TP53 exon mutations.SPSS 26.0 software was used to analyze the data, and P &lt; 0.05 indicated statistical difference. Results: The frequency of single gene mutation in 314 patients was analyzed. The most common mutation was TP53 (64.3%), followed by EGFR (49.4%).TP53wt group compared with TP53mut group OS (34.3m vs 28.9m; HR = 1.263, 95% ci: 0.933 1.709;P = 0.131).The OS of Exon4 group was 23 months, Exon8 group was 44.5 months, and TP53wt group was 34.3 months, no statistical significance was observed (P = 0.159).In the TP53/KRAS co-mutation group, the median OS of KRAS/TP53 (mut/mut) group and KRAS/TP53 (wt/wt) group was 29.4m vs 34.3m; HR = 2.482, 95%Cl:1.378-4.471, P = 0.002).In subgroup analysis, the median OS of KRASG12Cmut/TP53mut group and KRASG12Cmut/TP53wt group were (8.9m vs 34.9m; HR = 38.268, 95%CL: 8.359-175.183, P = 0.199), (3.1m vs 34.3m; HR = 2.572, 95%Cl:1.344-4.922,P = 0.004).In the TP53/EGFR co-mutation group, the median OS of EGFRmut/TP53mut, EGFRwt/TP53mut, EGFRmut/TP53wt and EGFRwt/TP53wt were 32.9, 17.9, 42.7 and 31.2 months, respectively (P = 0.004).In subgroup analysis, the median OS of EGFRmut/ TP53Exon4-mut versus EGFRwt/TP53wt group was (25.8m vs 31.1m; HR = 2.909, 95%Cl: 1.438-5.886, P = 0.003). Conclusions: TP53 is a factor of poor prognosis in NSCLC patients, patients with TP53/KRAS co-mutation have poor survival, and kRASG12C-mut /TP53mut subgroup have worse prognosis.Patients with TP53/EGFR co-mutation had a better prognosis, and the EGFRmut/ TP53Exon4-mut subgroup had the worst prognosis.